Serotonin or 5-hydroxytryptamine or 5-HT is a vasoconstrictor and a powerful stimulant of a variety of smooth muscles and nerves. A derivative of the amino acid tryptophan, 5-HT is formed predominantly in enterochromaffin or argentaffin cells of the intestinal tract. It is transported in the blood by platelets and is present in the brain and other tissues. Its pharmacological actions result in a variety of responses involving, inter alia, the cardiovascular, respiratory, and gastrointestinal systems, smooth muscles, exocrine glands, carbohydrate metabolism, sensory nerve endings, autonomic ganglia, the adrenal medulla, and the central nervous system.
Receptors are molecules embedded in outer cell membranes, the main function of which are to recognize and interact with hormones that come in contact with the cell. They act as locks, while the hormones act as keys. Each key (hormone) fits the lock (receptor) that interacts with it and with it alone. Once the key (hormone) fits the lock (receptor), the reaction to the hormone is triggered within the cell. Cellular reaction is therefore determined by the type and number of receptors on the outer membrane of the cells. Consequently, one hormone can trigger different responses in different cells because it may have different receptors. Thus, the same hormone that can contract one smooth muscle cell, can also relax a skeletal muscle cell having a different receptor to the same hormone. This is true for 5-HT.
There are many receptors for 5-HT that control the various cellular responses which are mentioned above. To identify the different receptors to a specific hormone (e.g. 5-HT), several methods are used. For example, in labeling studies, the labeled hormone binds to a specific receptor. The antagonists are classified according to their ability to displace the labeled hormone from the receptor in question. Those that can displace it from a particular receptor are said to be antagonists to that receptor. Some antagonists can displace the hormone from one receptor without affecting its binding to another, and the degree of selectivity can thus be determined. In pharmacological studies, the ability of antagonists to antagonize some of the effects of the hormone thought to be related to one receptor or another are examined. A suitable example relates to the hormone histamine. Some antagonists (histamine-2 antagonists) can antagonize its acid secretory receptors with little or no effect on its lung receptors and thus inhibit acid secretion by the stomach without causing bronchodilatation. Other antagonists (histamine-1 antagonists) antagonize histamine's lung effects with almost no activity against its acid secretory effects. Biochemical studies are those in which the biochemical effects of the hormone in question can be antagonized selectively by one receptor antagonist or another.
Serotonin receptors are divided into several classes, one of which is referred to as the 5-HT.sub.2 receptor. A complete discussion of such receptors will be found in "The Peripheral Actions of 5-Hydroxytryptamine" edited by John R. Fozard (Oxford University Press, 1989). Based on a combination of the above studies, the 5-HT.sub.2 receptor has been identified, although some subclasses of it also seem to exist. Its binding to 5-HT is antagonized by specific 5-HT.sub.2 antagonists such as ketanserine and mesulergine. It acts by modulating phosphatidylinositol turnover, but this effect is inhibited by mianserin and ketanserin. It is present in the brain cortex, blood platelets and vascular smooth muscles. Stimulation of this receptor causes a detectable inward current due to elevated intracellular calcium ion levels in nervous tissue. It causes aggregation of the blood platelets and contraction of the vascular smooth muscles.
Hemorrhoids are a varicose dilatation of veins in the superior or inferior hemorrhoidal plexus. More commonly, hemorrhoids refer to a mass of dilated veins in swollen tissue situated near the anal sphincter. They are believed to result from a persistent increase in venous pressure, which may be due, in part, to a constriction of the large downstream colonic veins. Occlusion due to platelet aggregation and thrombus formation may also contribute to the symptoms of hemorrhoids by interrupting blood flow and increasing blood stasis and tissue congestion.
5-HT.sub.2 antagonist compounds have traditionally been used as anti-anxiety agents, antidepressants, antipsychotics, antimigraine agents or as modifiers of certain other CNS functions.